Training state and skeletal muscle autophagy in response to 36 h of fasting

Maja Munk Dethlefsen; Lærke Bertholdt; Anders Gudiksen; Tomasz Stankiewicz; Jens Bangsbo; Gerrit van Hall; Peter Plomgaard; Henriette Pilegaard

doi:10.1152/japplphysiol.01146.2017

Training state and skeletal muscle autophagy in response to 36 h of fasting

Maja Munk Dethlefsen, Lærke Bertholdt, Anders Gudiksen, Tomasz Stankiewicz, Jens Bangsbo, Gerrit van Hall, Peter Plomgaard, Henriette Pilegaard

3 Citations (Scopus)

Abstract

The present study aimed at investigating fasting-induced responses in regulators and markers of autophagy in vastus lateralis muscle from untrained and trained human subjects. Untrained and trained subjects (based on maximum oxygen uptake, muscle citrate synthase activity, and oxidative phosphorylation protein level) fasted for 36 h with vastus lateralis muscle biopsies obtained at 2, 12, 24, and 36 h after a standardized meal. Fasting reduced (P 0.05) skeletal muscle microtubule-associated protein-1A/1B light chain 3 (LC3)I, LC3II, and adaptor protein sequestosome 1/p62 protein content in untrained subjects only. Moreover, skeletal muscle RAC-alpha serine/threonine-protein kinase (AKT) ^Thr308, AMP-activated protein kinase (AMPK) ^Thr172, and Unc-51-like autophagy-activating kinase-1 (ULK1) ^Ser555 phosphorylation state, as well as Bcl-2-interacting coiled-coil protein-1 (Beclin1) and ULK1 ^Ser757 phosphorylation, was lower (P 0.05) in trained than untrained subjects during fasting. In addition, the plasma concentrations of several amino acids were higher (P 0.05) in trained than untrained subjects, and the plasma concentration profile of several amino acids was different in untrained and trained subjects during fasting. Taken together, these findings suggest that 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle and that training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle. NEW & NOTEWORTHY This study showed that skeletal muscle autophagy was only modestly affected in humans by 36 h of fasting. Hence, 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle, and training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle.

Original language	English
Journal	Journal of Applied Physiology
Volume	125
Issue number	5
Pages (from-to)	1609-1619
Number of pages	11
ISSN	8750-7587
DOIs	https://doi.org/10.1152/japplphysiol.01146.2017
Publication status	Published - Nov 2018

Keywords

Faculty of Science
Fasting
Exercise training
Skeletal muscle
Autophagy
Signaling
Plasma amino acid
Autophagy
Exercise training
Fasting
Plasma amino acid
Signaling
Skeletal muscle
autophagy
signaling
plasma amino acid
exercise training
fasting
skeletal muscle

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title = "Training state and skeletal muscle autophagy in response to 36 h of fasting",

abstract = "The present study aimed at investigating fasting-induced responses in regulators and markers of autophagy in vastus lateralis muscle from untrained and trained human subjects. Untrained and trained subjects (based on maximum oxygen uptake, muscle citrate synthase activity, and oxidative phosphorylation protein level) fasted for 36 h with vastus lateralis muscle biopsies obtained at 2, 12, 24, and 36 h after a standardized meal. Fasting reduced (P 0.05) skeletal muscle microtubule-associated protein-1A/1B light chain 3 (LC3)I, LC3II, and adaptor protein sequestosome 1/p62 protein content in untrained subjects only. Moreover, skeletal muscle RAC-alpha serine/threonine-protein kinase (AKT) Thr308, AMP-activated protein kinase (AMPK) Thr172, and Unc-51-like autophagy-activating kinase-1 (ULK1) Ser555 phosphorylation state, as well as Bcl-2-interacting coiled-coil protein-1 (Beclin1) and ULK1 Ser757 phosphorylation, was lower (P 0.05) in trained than untrained subjects during fasting. In addition, the plasma concentrations of several amino acids were higher (P 0.05) in trained than untrained subjects, and the plasma concentration profile of several amino acids was different in untrained and trained subjects during fasting. Taken together, these findings suggest that 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle and that training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle. NEW & NOTEWORTHY This study showed that skeletal muscle autophagy was only modestly affected in humans by 36 h of fasting. Hence, 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle, and training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle. ",

keywords = "Faculty of Science, Fasting, Exercise training, Skeletal muscle, Autophagy, Signaling, Plasma amino acid, Autophagy, Exercise training, Fasting, Plasma amino acid, Signaling, Skeletal muscle, autophagy, signaling, plasma amino acid, exercise training, fasting, skeletal muscle",

author = "Dethlefsen, {Maja Munk} and L{\ae}rke Bertholdt and Anders Gudiksen and Tomasz Stankiewicz and Jens Bangsbo and {van Hall}, Gerrit and Peter Plomgaard and Henriette Pilegaard",

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T1 - Training state and skeletal muscle autophagy in response to 36 h of fasting

AU - Dethlefsen, Maja Munk

AU - Bertholdt, Lærke

AU - Gudiksen, Anders

AU - Stankiewicz, Tomasz

AU - Bangsbo, Jens

AU - van Hall, Gerrit

AU - Plomgaard, Peter

AU - Pilegaard, Henriette

N1 - CURIS 2018 NEXS 406

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N2 - The present study aimed at investigating fasting-induced responses in regulators and markers of autophagy in vastus lateralis muscle from untrained and trained human subjects. Untrained and trained subjects (based on maximum oxygen uptake, muscle citrate synthase activity, and oxidative phosphorylation protein level) fasted for 36 h with vastus lateralis muscle biopsies obtained at 2, 12, 24, and 36 h after a standardized meal. Fasting reduced (P 0.05) skeletal muscle microtubule-associated protein-1A/1B light chain 3 (LC3)I, LC3II, and adaptor protein sequestosome 1/p62 protein content in untrained subjects only. Moreover, skeletal muscle RAC-alpha serine/threonine-protein kinase (AKT) Thr308, AMP-activated protein kinase (AMPK) Thr172, and Unc-51-like autophagy-activating kinase-1 (ULK1) Ser555 phosphorylation state, as well as Bcl-2-interacting coiled-coil protein-1 (Beclin1) and ULK1 Ser757 phosphorylation, was lower (P 0.05) in trained than untrained subjects during fasting. In addition, the plasma concentrations of several amino acids were higher (P 0.05) in trained than untrained subjects, and the plasma concentration profile of several amino acids was different in untrained and trained subjects during fasting. Taken together, these findings suggest that 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle and that training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle. NEW & NOTEWORTHY This study showed that skeletal muscle autophagy was only modestly affected in humans by 36 h of fasting. Hence, 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle, and training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle.

AB - The present study aimed at investigating fasting-induced responses in regulators and markers of autophagy in vastus lateralis muscle from untrained and trained human subjects. Untrained and trained subjects (based on maximum oxygen uptake, muscle citrate synthase activity, and oxidative phosphorylation protein level) fasted for 36 h with vastus lateralis muscle biopsies obtained at 2, 12, 24, and 36 h after a standardized meal. Fasting reduced (P 0.05) skeletal muscle microtubule-associated protein-1A/1B light chain 3 (LC3)I, LC3II, and adaptor protein sequestosome 1/p62 protein content in untrained subjects only. Moreover, skeletal muscle RAC-alpha serine/threonine-protein kinase (AKT) Thr308, AMP-activated protein kinase (AMPK) Thr172, and Unc-51-like autophagy-activating kinase-1 (ULK1) Ser555 phosphorylation state, as well as Bcl-2-interacting coiled-coil protein-1 (Beclin1) and ULK1 Ser757 phosphorylation, was lower (P 0.05) in trained than untrained subjects during fasting. In addition, the plasma concentrations of several amino acids were higher (P 0.05) in trained than untrained subjects, and the plasma concentration profile of several amino acids was different in untrained and trained subjects during fasting. Taken together, these findings suggest that 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle and that training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle. NEW & NOTEWORTHY This study showed that skeletal muscle autophagy was only modestly affected in humans by 36 h of fasting. Hence, 36-h fasting has effects on some mediators of autophagy in untrained human skeletal muscle, and training state influences the effect of fasting on autophagy signaling and on mediators of autophagy in skeletal muscle.

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KW - Signaling

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KW - Fasting

KW - Plasma amino acid

KW - Signaling

KW - Skeletal muscle

KW - autophagy

KW - signaling

KW - plasma amino acid

KW - exercise training

KW - fasting

KW - skeletal muscle

U2 - 10.1152/japplphysiol.01146.2017

DO - 10.1152/japplphysiol.01146.2017

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SN - 8750-7587

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EP - 1619

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

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ER -

Training state and skeletal muscle autophagy in response to 36 h of fasting

Abstract

Keywords

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